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Blood Glucose Regulation

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 Blood Glucose Regulation
 Blood glucose concentration narrowly controlled
between 80 and 90mg/100ml of blood in the
fasting state

 Increases to 120 to 140 mg/100ml during the first

hour or so after a meal

 Within 2 hours, Insulin and glucagon feedback

control system for control of blood glucose return
the glucose concentration back to the control level
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 Blood Glucose Regulation

 Liver as blood glucose buffer

 Fasting hypoglycemia stimulates glucagon from
pancreatic alpha cells
 Acute Severe hypoglycemia directly effects the
hypothalamus to stimulate sympathetic nervous
system
 Prolonged hypoglycemia stimulate both growth
hormone and cortisol secretion
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Summary: Blood Glucose Regulation

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 Diabetes Mellitus
"starvation in the midst of
plenty"

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 A syndrome of impaired carbohydrate, fat,
and protein metabolism caused by either
lack of insulin secretion or decreased
sensitivity of the tissues to insulin
 Three cardinal signs of DM :
 Polyuria –high urine output
 Polydipsia – excessive thirst
 Polyphagia – excessive hunger and food
consumption

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Two general types of diabetes mellitus:
1. Type I diabetes, also called Insulin-dependent
Diabetes Mellitus (IDDM): caused by lack of
insulin secretion
2. Type II diabetes, also called Non-insulin-
dependent Diabetes Mellitus (NIDDM): caused by
decreased sensitivity of target tissues to the
metabolic effect of insulin (Insulin Resistance)

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 The efficient uptake and utilization of glucose
by most cells of the body is prevented, except
those of the brain
As a result:
 Blood glucose concentration increases
 Cellular utilization of glucose falls
 Mobilization and utilization of fats and proteins
increases with concurrent hyperlipidemia and
hypercholesterolemia
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 Type – I Diabetes Mellitus
Lack of Insulin Production by Beta Cells
of the Pancreas
 Destruction of B cells
 Chronic Fasted State

Causes
 Viral Infection or autoimmune Disorders
 Hereditary Tendency
Also called Juvenile diabetes mellitus as onset
usually below the age 20

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 Type – I Diabetes Presentation

1. Increase blood glucose hyperglycemia (300-

1200mg/100ml

2. Increase utilization of fat leading to metabolic

Acidosis and ketosis with raised blood
cholesterol

3. Polyphagia

4. Depletion of body protein

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Type – I Diabetes Presentation:

5. Loss of glucose in urine (glycosuria)

6. Polyuria leading to both extracellular and intra

cellular dehydration – leading to polydipsia

7. Microvascular and macrovascular complications

like nephropathy, retinopathy, atherosclerosis

8. Autonomic and peripheral neuropathies

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 Diabetic Coma
 Increased utilization of fats increases the release of
ketoacids and leads to metabolic acidosis

 If untreated, leads rapidly to diabetic coma and death

 T/M is infusion of insulin and K+ replacement

Physiological compensations:

 Rapid and deep breathing: air hunger (Kussmaul

breathing)

 Kidneys decrease bicarbonate excretion and generate

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new bicarbonate
Changes in blood constituents in
diabetic coma, showing normal
values (lavender bars) and
diabetic coma values (red bars)

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Type– II Diabetes: Resistance to the
Metabolic Effects of Insulin

 More common than type – I (90%)

 Occurs usually after age 30 and between 50 and

60 years, called Adult Onset Diabetes

 Obesity: leading risk factor

 Obesity, Insulin Resistance, and “Metabolic

Syndrome” precede Type – II diabetes
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 Insulin Resistance
 Insulin resistance keeps blood glucose too high

 Compensatory hyperinsulinemia

 In the later stages, the pancreatic beta cells

become "exhausted" and are unable to produce
sufficient insulin

 Chronic complications: atherosclerosis, renal

failure & blindness
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 Obesity and “Metabolic
Syndrome”
 Metabolic syndrome
1. Obesity with accumulation of abdominal fat

2. Insulin resistance

3. Hyperinsulinemia

4. Fasting hyperglycemia

5. Increased blood triglycerides and HDL

6. Hypertension
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 The mechanisms that link obesity
with insulin resistance

 Fewer insulin receptors, especially in the

skeletal muscle, liver, and adipose tissue, in
obese than in lean subjects

 Abnormalities of the signaling pathways

Toxic effects of lipid accumulation in insulin

sensitive tissues such as skeletal muscle
and liver secondary to obesity 24
Skeletal Muscle Insulin Resistance: Roles of Fatty Acid
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 Other factors that cause insulin
resistance and type II diabetes:
1. Polycystic ovary syndrome

2. Cushing’s syndrome

3. Acromegaly

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 Physiology of Diagnosis of
Diabetes Mellitus
1. Urinary glucose
2. Fasting blood glucose level and insulin
levels
3. Acetone breath
4. Glucose tolerance test

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Glucose tolerance test

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 Treatment of Diabetes
 Type – I Diabetes Mellitus
 Replacement of insulin
 Available in several forms
 Human insulin produced by the recombinant DNA
process
 Fast-acting, short-acting, intermediate-acting,
long acting and Combination insulin products
(characterized by the rate which they are
metabolized by the body)
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 Hypoglycaemia In Type 1 Diabetes
 There may be loss of ability to secrete glucagon in
response to low blood sugar, making patients
prone to severe hypoglycemia

 Glucagon Emergency Kit

 Glucagon works by making the liver convert

glycogen stores into glucose

 Effectiveness depends upon glycogen stores

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Physiological Compensatory
Mechanisms
 Cessation of the secretion of endogenous insulin at a
plasma glucose level of about 80 mg/dL

 Increased secretion of counter-regulatory hormones:

glucagon, epinephrine, growth hormone, and cortisol

 Glucagon and epinephrine increase the hepatic output of

glucose by increasing glycogenolysis

 Growth hormone and cortisol decreases the utilization of

glucose in various peripheral tissues

 Long term diabetics may suffer from “ hypoglycemia38

unawareness”
Treatment of Diabetes Type – II
 Life Style Modification: Total caloric intake control and
exercise

 Oral hypoglycemic agents: either decrease the insulin

resistance (thiazolidinediones,
Metformin or Glucophage) or increase the insulin
production by β cells (sulphonylureas)

 Lipid lowering drugs for treatment of atherosclerosis

 Regular monitoring of serum glucose, HbA1c, and low-

density lipoprotein (LDL) cholesterol levels 39
Insulinoma – Hyperinsulinism

 Excessive insulin production from adenoma of

an islet of Langerhans
 Blood glucose level may be so low that more
than 1000 gm of glucose/day is needed
 Insulin Shock: the metabolism of the central
nervous system becomes depressed with very
high levels of insulin (blood glucose may fall
below 20 mg/100 ml)
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 Coma results
 Diabetic Acidotic Coma (as a result of insulin-lack)
Versus
Hypoglycemic Coma (caused by excess insulin)

 Medical emergency

 Immediate intravenous administration 10% dextrose, if

hypoglycaemic shock, immediate revival

 If not treated immediately, permanent damage to the

neuronal cells of the central nervous system

 Help-tip:The acetone breath and Kussmaul breathing

of diabetic coma are not present in hypoglycemic coma
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 Thank you

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